Effects of amphetamine on brain energy metabolism and protein synthesis are being investigated under conditions which give rise to changes in body temperature in response to the drug. In particular, metabolic changes associated with drug induced hyperthermia are being correlated with the hyperthermia-dependent inhibition of brain protein synthesis by amphetamine. Effects on protein synthesis are determined by means of brain polyribosome profiles. Metabolites of interest include brain glucose, glycogen and high-energy phosphates, especially guanine nucleotides, which are measured enzymatically. Hyperthermia-associated effects on all of the above metabolites have been demonstrated following amphetamine administration. The preciously observed brain glycogenolysis induced by amphetamine has now been found to be correlated with hyperthermia in response to the drug. Significant reductions in brain GTP levels during amphetamine-induced hyperthermia may be responsible in part for the inhibiyion of brain protein synthesis which is also observed.